The highly reducing sugar 2-deoxy-D-ribose induces apoptosis in human fibroblasts by reduced glutathione depletion and cytoskeletal disruption.
2-deoxy-D-Ribose (dRib), the most reducing sugar, induces apoptosis in normal human fibroblasts, as judged by cytoplasmic shrinkage, chromatin condensation, DNA fragmentation and mitochondrial depolarization. This effect is independent from culture conditions, such as cell density and the presence or absence of serum in the culture milieu, suggesting that dRib-induced apoptosis is cell cycle-independent. dRib was found also to provoke disruption of the actin filament network and detachment from the substratum, while at the same time, interestingly, it increases the expression of several integrins and cell adhesion molecules. Furthermore, dRib was found to reduce the intracellular levels of reduced glutathione (GSH). The apoptotic process was not affected by the macromolecular-synthesis inhibitors cycloheximide and actinomycin D. On the contrary, the antioxidant N-acetyl-L-cysteine (NAC) fully blocks the dRib-induced apoptosis by preventing GSH depletion, while it also inhibits actin-filament-network disruption and mitochondrial depolarization. The above indicate that dRib induces apoptosis in human fibroblasts by a mechanism involving glutathione metabolism and oxidative stress, as well as disturbance of cytoskeletal integrity and cell adhesion.
Kletsas
D
D
Institute of Biology, N.C.S.R. Demokritos, Athens, Greece. dikl3@cyclades.nrcps.ariadne-t.gr
Barbieri
D
D
Stathakos
D
D
Botti
B
B
Bergamini
S
S
Tomasi
A
A
Monti
D
D
Malorni
W
W
Franceschi
C
C
D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000032:analysis; D002452:Cell Count / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects*; D003855:Deoxyribose / Q000494:pharmacology* / Q000633:toxicity; D005347:Fibroblasts; D005434:Flow Cytometry; D005978:Glutathione / Q000032:analysis / Q000172:deficiency*; D006801:Humans; D016023:Integrins / Q000032:analysis; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D002843:Chromatin; D016023:Integrins; D011500:Protein Synthesis Inhibitors; D003855:Deoxyribose; D005978:Glutathione; D000111:Acetylcysteine